Enzymatic Enantioselective anti‐Markovnikov Hydration of Aryl Alkenes

Abstract The addition of water to alkenes is an important method for the synthesis of alcohols, but the regioselectivity of acid‐catalyzed hydration of terminal alkenes yields secondary alcohols according to Markovnikov's rule, making it difficult to obtain primary alcohols. Here we report a styrene monooxygenase that catalyzes the anti‐Markovnikov hydration of the terminal aryl alkenes under anaerobic conditions. This hydration provides primary alcohols in good yields (up to 100 %), excellent anti‐Markovnikov regioselectivity (>99 : 1), and good enantiomeric purity (60–83 % ee). Residues Asn46, Asp100, and Asn309 are essential for catalysis suggesting an acid–base mechanism with a carbanion‐like intermediate that could account for the anti‐Markovnikov regioselectivity. Our work reveals a new enzymatic tool with unusual regioselectivity based on the promiscuous catalytic activity of a monooxygenase.